Kai Zhang
Publications
BioMiner: A Multi-modal System for Automated Mining of Protein-Ligand Bioactivity Data from Literature
Protein-ligand bioactivity data published in the literature are essential for drug discovery, yet manual curation struggles to keep pace with rapidly growing literature. Automated bioactivity extraction remains challenging because it requires not only interpreting biochemical semantics distributed across text, tables, and figures, but also reconstructing chemically exact ligand structures (e.g., Markush structures). To address this bottleneck, we introduce BioMiner, a multi-modal extraction framework that explicitly separates bioactivity semantic interpretation from ligand structure construction. Within BioMiner, bioactivity semantics are inferred through direct reasoning, while chemical structures are resolved via a chemical-structure-grounded visual semantic reasoning paradigm, in which multi-modal large language models operate on chemically grounded visual representations to infer inter-structure relationships, and exact molecular construction is delegated to domain chemistry tools. For rigorous evaluation and method development, we further establish BioVista, a comprehensive benchmark comprising 16,457 bioactivity entries curated from 500 publications. BioMiner validates its extraction ability and provides a quantitative baseline, achieving an F1 score of 0.32 for bioactivity triplets. BioMiner's practical utility is demonstrated via three applications: (1) extracting 82,262 data from 11,683 papers to build a pre-training database that improves downstream models performance by 3.9%; (2) enabling a human-in-the-loop workflow that doubles the number of high-quality NLRP3 bioactivity data, helping 38.6% improvement over 28 QSAR models and identification of 16 hit candidates with novel scaffolds; and (3) accelerating protein-ligand complex bioactivity annotation, achieving a 5.59-fold speed increase and 5.75% accuracy improvement over manual workflows in PoseBusters dataset.
Layer-Order Inversion: Rethinking Latent Multi-Hop Reasoning in Large Language Models
Large language models (LLMs) perform well on multi-hop reasoning, yet how they internally compose multiple facts remains unclear. Recent work proposes \emph{hop-aligned circuit hypothesis}, suggesting that bridge entities are computed sequentially across layers before later-hop answers. Through systematic analyses on real-world multi-hop queries, we show that this hop-aligned assumption does not generalize: later-hop answer entities can become decodable earlier than bridge entities, a phenomenon we call \emph{layer-order inversion}, which strengthens with total hops. To explain this behavior, we propose a \emph{probabilistic recall-and-extract} framework that models multi-hop reasoning as broad probabilistic recall in shallow MLP layers followed by selective extraction in deeper attention layers. This framework is empirically validated through systematic probing analyses, reinterpreting prior layer-wise decoding evidence, explaining chain-of-thought gains, and providing a mechanistic diagnosis of multi-hop failures despite correct single-hop knowledge. Code is available at https://github.com/laquabe/Layer-Order-Inversion.